The growing success of organ transplantation for the treatment of diabetes mellitus and end-stage renal, heart, lung, and liver disease is attributable, in part, to improvements in immunosuppressive regimens. This article reviews the immune response and the mechanism by which many immunosuppressants exert their effects. Immunosuppressants discussed include azathioprine, glucocorticoids, cyclosporine A, cyclosporine G, FK506, rapamycin, mycophenolic acid, mycophenolate mofetil (RS-61443), mizoribine (bredinin), brequinar sodium, and deoxyspergualine. The efficacy and nonspecificity of these agents has led to significant side effects from their use, which can be predicted based on their mechanisms of action. The development and use of more specific immunosuppressants or the design of protocols, which would induce organ tolerance, may result in long-term organ survival without infectious or malignant complications.